The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites

Cellular homeostasis depends on robust protein quality control (PQC) pathways that discern misfolded proteins from functional ones in the cell. One major branch of PQC involves the controlled degradation of misfolded proteins by the ubiquitin-proteasome system. Here ubiquitin ligases must recognize...

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Autores principales:	Rebeca Ibarra, Heather R. Borror, Bryce Hart, Richard G. Gardner, Gary Kleiger
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	protein quality control ubiquitylation protein degradation ubiquitin ligase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/84c914f5f0ea47cb9945cc10aa9a52e0
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id	oai:doaj.org-article:84c914f5f0ea47cb9945cc10aa9a52e0
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spelling	oai:doaj.org-article:84c914f5f0ea47cb9945cc10aa9a52e02021-11-25T16:52:52ZThe San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites10.3390/biom111116192218-273Xhttps://doaj.org/article/84c914f5f0ea47cb9945cc10aa9a52e02021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1619https://doaj.org/toc/2218-273XCellular homeostasis depends on robust protein quality control (PQC) pathways that discern misfolded proteins from functional ones in the cell. One major branch of PQC involves the controlled degradation of misfolded proteins by the ubiquitin-proteasome system. Here ubiquitin ligases must recognize and bind to misfolded proteins with sufficient energy to form a complex and with an adequate half-life to achieve poly-ubiquitin chain formation, the signal for protein degradation, prior to its dissociation from the ligase. It is not well understood how PQC ubiquitin ligases accomplish these tasks. Employing a fully reconstituted enzyme and substrate system to perform quantitative biochemical experiments, we demonstrate that the yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain that appear to display specificity for unique misfolded proteins. The results are consistent with a model where these substrate binding sites enable San1 to bind to misfolded substrates avidly, resulting in high affinity ubiquitin ligase-substrate complexes.Rebeca IbarraHeather R. BorrorBryce HartRichard G. GardnerGary KleigerMDPI AGarticleprotein quality controlubiquitylationprotein degradationubiquitin ligaseMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1619, p 1619 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	protein quality control ubiquitylation protein degradation ubiquitin ligase Microbiology QR1-502
spellingShingle	protein quality control ubiquitylation protein degradation ubiquitin ligase Microbiology QR1-502 Rebeca Ibarra Heather R. Borror Bryce Hart Richard G. Gardner Gary Kleiger The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
description	Cellular homeostasis depends on robust protein quality control (PQC) pathways that discern misfolded proteins from functional ones in the cell. One major branch of PQC involves the controlled degradation of misfolded proteins by the ubiquitin-proteasome system. Here ubiquitin ligases must recognize and bind to misfolded proteins with sufficient energy to form a complex and with an adequate half-life to achieve poly-ubiquitin chain formation, the signal for protein degradation, prior to its dissociation from the ligase. It is not well understood how PQC ubiquitin ligases accomplish these tasks. Employing a fully reconstituted enzyme and substrate system to perform quantitative biochemical experiments, we demonstrate that the yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain that appear to display specificity for unique misfolded proteins. The results are consistent with a model where these substrate binding sites enable San1 to bind to misfolded substrates avidly, resulting in high affinity ubiquitin ligase-substrate complexes.
format	article
author	Rebeca Ibarra Heather R. Borror Bryce Hart Richard G. Gardner Gary Kleiger
author_facet	Rebeca Ibarra Heather R. Borror Bryce Hart Richard G. Gardner Gary Kleiger
author_sort	Rebeca Ibarra
title	The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
title_short	The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
title_full	The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
title_fullStr	The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
title_full_unstemmed	The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites
title_sort	san1 ubiquitin ligase avidly recognizes misfolded proteins through multiple substrate binding sites
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/84c914f5f0ea47cb9945cc10aa9a52e0
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The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites

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